Drug-induced acute interstitial nephritis (AIN) is an important but often under-recognized cause of acute kidney injury (AKI), particularly in patients treated empirically for presumed infection. In clinical practice, improvement in fever and systemic symptoms may give false reassurance while kidney injury continues to progress. This is especially relevant in patients with pre-existing chronic kidney disease (CKD), where delayed recognition may lead to dialysis-requiring AKI despite a potentially reversible pathology.

A 63-year-old man with diabetes mellitus, hypertension, gout, and baseline stage 3a CKD presented with 10 days of fever and chills after recent travel. He was initially treated for presumed occult sepsis with sequential beta-lactam antibiotics and supportive inpatient medications including proton pump inhibitor therapy. Although fever and systemic symptoms improved, serum creatinine rose rapidly from a baseline of 120–140 µmol/L to 773 µmol/L, prompting nephrology referral.

The patient developed metabolic acidosis and required temporary hemodialysis. Autoimmune testing showed elevated erythrocyte sedimentation rate and positive antinuclear antibody, raising concern for systemic autoimmune disease; however, complements were normal and subsequent urinalysis was relatively bland. Given the mismatch between systemic recovery and renal deterioration, kidney biopsy was performed. Histology showed eosinophil-rich interstitial inflammation with lymphocytes, plasma cells, and acute tubular injury, consistent with drug-induced AIN. No crescentic, proliferative, or immune-complex glomerular lesion was identified. Suspected offending agents were withdrawn and corticosteroid therapy was started. The patient was liberated from hemodialysis after two sessions, with creatinine improving to 242 µmol/L and subsequently returning near baseline at 140.7 µmol/L.

This case illustrates that clinical improvement after presumed sepsis does not exclude ongoing drug-induced kidney injury. In severe unexplained AKI, particularly in patients with CKD and multiple drug exposures, early kidney biopsy can clarify the diagnosis, redirect treatment, and support renal recovery. The key lesson is practical: when the systemic picture improves but the kidney continues to fail, the renal trajectory should drive decision-making.